The gene variants among different modern ethnic groups are all subsets of our ancestral African gene pool. Table 1. Key Concepts 1. Genetics is the study of inherited traits and their variation. Genetics can be considered at the levels of DNA, genes, chromosomes, genomes, cells, tissues, organs, individuals, families, and populations.
A gene can exist in more than one form, or allele. Comparing genomes among species reveals evolutionary relatedness. These are called single-gene or Mendelian traits. This may have been an overly simple view. Most genes do not function alone but are influenced by the actions of other genes, as well as by factors in the environment. For example, a number of genes control how we metabolize nutrients—that is, how much energy calories we extract from food. However, the numbers and types of bacteria that live in our intestines vary from person to person, and these microbes affect how many calories we extract from food.
This is one reason why some people can eat a great deal and not gain weight, yet others gain weight easily. Multifactorial, or complex, traits are those that are determined by one or more genes and the environment figure 1.
The term complex traits has different meanings in a scientific and a popular sense, so this book uses the more precise term multifactorial.
Complicating matters further is the fact that some illnesses occur in different forms— they may be inherited or not, and if inherited, may be caused by one gene or more than one. Researchers can develop treatments based on the easier-to-study inherited form of an illness that can then be used to treat the more common, multifactorial forms.
For example, cholesterol-lowering drugs were developed from work on the one-in-a-million children with familial hypercholesterolemia OMIM see figure 5. Genes and Disease Risk Knowing whether a trait or illness is single-gene or multifactorial is important for predicting the risk of recurrence. The probability that a single-gene trait will occur in a particular family member is simple to calculate using the laws that Mendel derived, discussed in chapter 4.
In contrast, predicting the recurrence of a multifactorial trait is difficult because several contributing factors are at play.
One form of inherited breast cancer illustrates how the fact that genes rarely act alone can complicate the calculation of risk.
In Jewish families of eastern European descent Ashkenazim , the most common BRCA1 mutation confers an 86 percent chance of developing the disease over a lifetime.
But women from other ethnic groups who inherit this allele have only a 45 percent chance. The different incidence of disease associated with inheriting the same gene, depending 8 b. Incidence refers to the frequency of a condition in a population. Prevalence refers to how common a condition is in a particular area at a particular time.
For example, exposure to pesticides that mimic the effects of the hormone estrogen may contribute to causing breast cancer. It can be difficult to tease apart these genetic and environmental influences.
This population includes both many Ashkenazim and many people exposed to pesticides. Genetic Determinism The fact that the environment modifies gene actions counters the idea of genetic determinism, which is that an inherited trait is inevitable. In predictive testing for inherited disease, which detects a diseasecausing allele in a person without symptoms, results are presented as risks, rather than foregone conclusions, because the environment can modify gene expression.
Genetic determinism may be harmful or helpful, depending upon how we apply it. As part of social policy, genetic determinism can be disastrous. Environment, in fact, has a huge impact on intellectual development. Identifying the genetic component to a trait can, however, be helpful in that it gives us more control over our health by guiding us in influencing noninherited factors, such as diet.
This is the case for the gene that encodes a liver enzyme called hepatic lipase. Inherit one allele and a person can eat a fatty diet yet have a healthy cholesterol profile. Inherit a different allele and a slice of chocolate cake or a fatty burger sends LDL up and HDL down—an unhealthy cholesterol profile. Inherited traits are determined by one gene Mendelian or by one or more genes and the environment multifactorial. Even the expression of single genes is affected to some extent by the actions of other genes.
Genetic determinism is the idea that an inherited trait cannot be modified. Genetics is impacting many areas of our lives, from health care choices, to what we eat and wear, to unraveling our pasts and controlling our futures. Thinking about genetics evokes fear, hope, anger, and wonder, depending on context and circumstance. Following are glimpses of applications of genetics that we will explore more fully in subsequent chapters.
This approach, called DNA profiling, has many applications. Forensics Before September 11, , the media reported on DNA profiling also known as DNA fingerprinting rarely, usually to identify plane crash victims or to provide evidence in high-profile criminal cases. After the terrorist attacks, investigators compared DNA sequences in bone and teeth collected from the scenes to hair and skin samples from hairbrushes, toothbrushes, and clothing of missing people, and to DNA samples from relatives.
It was a massive undertaking that would soon be eclipsed by two natural disasters—to identify victims of the tsunami in Asia in and hurricane Katrina in the United States in A more conventional forensic application matches a rare DNA sequence in tissue left at a crime scene to that of a sample from a suspect.
This is statistically strong evidence that the accused person was at the crime scene or that someone planted evidence. This is especially helpful when there is no suspect. DNA profiling is used to overturn convictions, too. Illinois has led the way; there, in , DNA tests exonerated the Ford Heights Four, men convicted of a gang rape and double murder who had spent eighteen years in prison, two of them on death row.
A journalism class at Northwestern University initiated the investigation that gained the men their freedom.
The case led to new state laws granting death row inmates new DNA tests if their convictions could have arisen from mistaken identity, or if DNA tests were performed when they were far less accurate. In , Governor George Ryan was so disturbed by the number of overturned convictions based on DNA evidence that shortly before he left office, he commuted the sentences of everyone on death row to life imprisonment.
DNA profiling helps adopted individuals locate blood relatives. Adopted individuals can provide a DNA sample and search the database by country of origin to find siblings. Rewriting History DNA analysis can help to flesh out details of history. Rumor at the time placed Jefferson near Hemings nine months before each of her seven children was born, and the children themselves claimed to be presidential offspring. The Y chromosome, because it is only in males, passes from father to son. Reaching farther back, DNA profiling can clarify relationships from Biblical times.
Consider a small group of Jewish people, the cohanim, who share distinctive Y chromosome DNA sequences and enjoy special status as priests. By considering the number of DNA differences between cohanim and other Jewish people, how long it takes DNA to mutate, and the average generation time of 25 years, researchers extrapolated that the cohanim Y chromosome pattern originated 2, to 3, years ago—which includes the time when Moses lived.
Researchers looked at them for the telltale gene variants because their customs suggest a Jewish origin—they do not eat pork or hippopotamus , they circumcise their newborn sons, and they celebrate a weekly day of rest figure 1. DNA profiling can trace origins for organisms other than humans.
For example, researchers analyzed DNA from the leaves of varieties of wine grapes, in search of the two parental strains that gave rise Figure 1. After DNA evidence showed that Thomas Jefferson likely fathered a son of his slave, descendants of both sides of the family met. The Lemba, a modern people with dark skin, have the same Y chromosome DNA sequences as the cohanim, a group of Jewish priests.
One parent, known already, was the bluish-purple Pinot grape. Thanks to DNA analysis, vintners now know which parental stocks to preserve. Health Care Looking at disease from a genetic point of view is changing health care. In the past, physicians encountered genetics only as extremely rare disorders caused by single genes.
Today, medical science is increasingly recognizing the role that genes play not only in many common conditions, but also in how people react to drugs. Disease is beginning to be seen as the consequence of complex interactions among genes and environmental factors.
In applying genetics to common disorders, it helps to consider how inherited illness caused by a single gene differs from 10 a Gouais blanc and b Pinot noir grapes gave rise to nineteen modern popular wines, including chardonnay.
First, we can predict the recurrence risk for singlegene disorders using the laws of inheritance chapter 4 describes. In contrast, an infectious disease requires that a pathogen pass from one person to another—a much less predictable circumstance. A second key distinction of inherited illness is that the risk of developing symptoms can often be predicted. This is because all genes are present in all cells, even if they are not expressed in every cell.
The use of genetic testing to foretell disease is termed predictive medicine. For example, some women who have lost several young relatives to BRCA1 breast cancer and learn that they have inherited the mutation have their Table 1.
Risk can be predicted for family members. Predictive presymptomatic testing may be possible. Different populations may have different characteristic disease frequencies.
Correction of the underlying genetic abnormality may be possible. A medical diagnosis, however, is still based on symptoms or observable pathology, such as abnormal cells. This is because some people who inherit mutations associated with particular symptoms never actually develop them. A third feature of genetic disease is that an inherited disorder may be much more common in some populations than others.
The reason for such disease clustering is that we tend to pick partners in nonrandom ways, keeping mutations in certain populations. So far, tests can identify about 1, single-gene disorders, but each year, only about , people in the United States take these tests.
Many people fear that employers or insurers will discriminate based on the results of genetic tests—or even for taking the tests. Yet millions of people regularly have their cholesterol checked! In the United States, legislation to prevent the misuse of genetic information in the insurance industry has been in development since The Health Insurance Portability and Accountability Act HIPAA stated that genetic information, without symptoms, does not constitute a preexisting condition, and that individuals could not be excluded from group coverage on the basis of a genetic predisposition.
The law did not cover individual insurance policies, nor did it stop insurers from asking people to have genetic tests. In , U. President Bill Clinton issued an executive order prohibiting the federal government from obtaining genetic information for employees or job applicants and from using such information in promotion decisions. Still, many people continue to fear the misuse of genetic information. Some people take genetic tests under false names or do not allow test results to become part of their medical records or are afraid to participate in clinical trials of new treatments.
Genetic tests may actually, eventually, lower health care costs. If people know their inherited risks, they can forestall or ease symptoms that environmental factors might trigger—for example, by eating healthy foods, not smoking, exercising regularly, avoiding risky behaviors, having frequent medical exams, and beginning treatment earlier. A few genetic diseases can be treated. Supplying a missing protein can prevent some symptoms, such as providing a clotting factor to a person who has a bleeding disorder.
Gene therapy replaces instructions for producing the protein in the cells that are affected in the illness. To study how this rare disorder unfolds during development, which cannot be done on human embryos and fetuses, researchers used a well-studied roundworm. It has a gene very similar in DNA sequence to the human lissencephaly gene.
When mutant, the gene causes worms to have seizures! Agriculture The field of genetics arose from agriculture. Traditional agriculture is the controlled breeding of plants and animals to select individuals with certain combinations of inherited traits that are useful to us, such as seedless fruits or lean meat.
Biotechnology, the use of organisms to produce goods including foods and drugs or services, is an outgrowth of agriculture. One ancient example of biotechnology is using microorganisms to ferment fruits to manufacture alcoholic beverages, a technique the Babylonians used by B. Traditional agriculture is imprecise because it shuffles many genes—and, therefore, many traits—at a time.
In contrast, the application of DNA-based techniques, part of modern biotechnology, enables researchers to manipulate one gene at a time. This adds control and precision that is not part of traditional agriculture. If the organism has genes from another species, it is termed transgenic. Golden rice, for example, manufactures twenty-three times as much beta carotene a vitamin A precursor as unaltered rice.
Golden rice also stores twice as much iron as unaltered rice because one of its own genes is overexpressed. These nutritional boosts bred into edible rice strains may help prevent vitamin A and iron deficiencies in people who eat them. People in the United States have been safely eating GM foods for more than a decade.
In Europe, many people object to GM foods, on ethical grounds or based on fear. A public opinion poll in the United Kingdom discovered, for example, that a major reason citizens avoid GM foods is that they do not want to eat DNA!
One British geneticist wryly observed that the average meal provides , kilometers about 93, miles of DNA. Other concerns about GM organisms may be better founded. Another objection is that field tests may not adequately predict the effects of GM crops on ecosystems. GM plants have been found far beyond where they were planted, thanks to wind pollination.
GM crops may also lead to extreme genetic uniformity, which could be disastrous. Some GM organisms, such as fish that grow to twice normal size or can survive at temperature extremes, may be so unusual that they disrupt ecosystems.
Ecology We humans share the planet with many thousands of other species. This information is revealing how species interact, and it may even yield new drugs and reveal novel energy sources. Metagenomics researchers collect and sequence DNA and consult databases of known genes and genomes to imagine what the organisms might be like.
One of the first metagenomics projects discovered and described life in the Sargasso Sea. Artist Alexis Rockman vividly captures some fears of biotechnology, including a pig used to incubate spare parts for sick humans, a muscle-boosted, boxy cow, a featherless chicken with extra wings, a mini-warthog, and a mouse with a human ear growing out of its back. Many a vessel has been lost in the Sargasso Sea, which includes the area known as the Bermuda Triangle.
When researchers sampled the depths, they collected more than a billion DNA bases, representing about 1, microbial species, including at least not seen before. More than a million new genes were discovered. Another metagenomics project is collecting DNA from air samples taken in lower Manhattan. A favorite site for metagenomics analysis is the human body.
The mouth, for example, is home to some species of bacteria, only about of which can grow in the laboratory. In addition to describing the ecosystem of the human mouth, metagenomics yields medically useful information. This was the case for Treponema denticola, which holds a place in medical history as the first microorganism that the father of microscopy, Antonie van Leeuwenhoek, sketched in the s.
Its genome revealed how it survives amid the films formed by other bacteria in the mouth, and how it causes gum disease. Researchers were surprised to find that this 12 microorganism is genetically very different from other spiral-shaped bacteria thought to be close relatives—those that cause syphilis and Lyme disease. Therefore, genomics showed that appearance a spiral shape does not necessarily reflect the closeness of the evolutionary relationship between two types of organisms.
Metagenomic analysis of the human digestive tract is also interesting at its other end. Analysis of the DNA in stool reveals hundreds of bacterial species. Based on such studies of various body parts, researchers conclude that 90 percent of the cells in the human body counting the digestive tract are not actually human! This is possible because microbial cells are so much smaller than ours. A Global Perspective Because genetics so intimately affects us, it cannot be considered solely as a branch of life science.
Equal access to testing, misuse of information, and abuse of genetics to intentionally cause harm are compelling issues that parallel scientific progress. Genetics and genomics are spawning technologies that may vastly improve quality of life. But at first, tests and treatments will be costly and not widely available. While advantaged people in economically and politically stable nations may look forward to genome-based individualized health care, poor people in other nations just try to survive, often lacking basic vaccines and medicines.
In an African nation where two out of five children suffer from AIDS and many die from other infectious diseases, newborn screening for rare single-gene defects hardly seems practical. However, genetic disorders weaken people so that they become more susceptible to infectious diseases, which they can pass to others. Human genome information can ultimately benefit everyone.
Consider drug development. Today, there are fewer than types of drugs. Genome information from humans and our pathogens and parasites is revealing new drug targets. For example, malaria is an infectious disease caused by a single-celled parasite transmitted through the bite of a female mosquito.
The genomes of the parasite, mosquito, and human have been sequenced, and within this vast amount of information likely lie clues that researchers can use to develop new types of anti-malarial drugs. Global organizations, including the United Nations, World Health Organization, and the World Bank, are discussing how nations can share new diagnostic tests and therapeutics that arise from genome information. The human genome belongs to us all. Genetics has applications in diverse areas.
Matching DNA sequences can clarify relationships, which is useful in forensics, establishing identity, and understanding historical events. Inherited disease differs from other disorders in its predictability; predictive testing; characteristic frequencies in different populations; and the potential of gene therapy.
Agriculture, both traditional and biotechnological, applies genetic principles. Collecting DNA from habitats and identifying the sequences in databases is a new way to analyze ecosystems. Human genome information has tremendous potential but must be carefully managed. A few days later, results are reported—but often without any guidance as to what they mean and sometimes accompanied by advice to purchase pricy supplements!
Such tests detect health-related gene variants most likely to be present in a particular individual, based on clues such as personal health, family history, and ethnic background.
This is what two year-old college roommates, Mackenzie and Laurel, decide to do. Mackenzie requests three panels of tests, based on her family background. Older relatives on both sides have Alzheimer disease. Mackenzie has tests to detect genes that predispose her to developing addictions, certain cancers, and inherited forms of Alzheimer disease.
Laurel requests different tests. She, her sister, and her mother frequently have bronchitis and pneumonia, so she has a test for cystic fibrosis CF OMIM , which can increase susceptibility to respiratory infections. She also has tests for type 2 diabetes mellitus because relatives have it, and diet and exercise can help control symptoms. Laurel refuses a test for inherited susceptibility to Alzheimer disease, even though a grandfather died of it.
Each student proceeds through several steps. The first is to record a complete family history. Next, each student rubs a cotton swab on the inside of her cheek to obtain cells, which are sent to a laboratory for analysis. There, DNA is cut up and displayed on a tiny device called a microarray that reveals the gene variants that are present or active.
Microarrays test many genes and are customized to individuals. After the test results are in, a genetic counselor explains the findings.
Mackenzie is predisposed to develop addictive behaviors and lung cancer—a dangerous combination—but she does not face increased risk for inherited forms of colon cancer or Alzheimer disease. Laurel has mild CF, which explains her frequent respiratory infections. The microarray indicates which types of infections she is most susceptible to, and which antibiotics will most effectively treat them.
The results also indicate which cholesterol-lowering drug will work best, should diet and exercise habits not be enough to counter her inherited tendency to accumulate lipids in the bloodstream.
Mackenzie and Laurel can take additional genetic tests as their interests and health status change. For example, they might take further tests when they and their partners are considering having a child, or if they become ill with cancer. Genetic tests can detect whether they are carriers for any of several hundred illnesses, because two carriers of the same condition can pass it to offspring even when they are not themselves affected.
If either Laurel or Mackenzie is in this situation, then tests on DNA from an embryo or a fetus can determine whether it has inherited the condition. Illness may prompt Laurel or Mackenzie to seek further testing. If either young woman suspects she may have cancer, for example, a type of microarray called an expression panel can determine which genes are turned on or off in the affected cells sampled from the tumor or from blood. In contrast, DNA from cheek lining cells reveals specific gene variants and DNA sequences that are present in all cells of the body.
DNA expression microarrays are very useful in diagnosing and treating cancer. They can identify cancer cells very early, when treatment is more likely to work, estimate if and how quickly the disease will progress, and even indicate which drugs are likely to be effective and which will likely produce intolerable side effects. Laws prevent employers and insurers from discriminating based on genetic information.
In general, insurance companies decide whom to insure and at what rates based on symptoms present before or at the time of request for coverage. The results of genetic tests are not clinical diagnoses or even predictions, but probability statements about how likely certain symptoms are to arise in an individual. Genes are the instructions to manufacture proteins, which determine inherited traits. A genome is a complete set of genetic information. A cell contains two genomes of DNA.
Genomics is the study of many genes and their interactions. Genes encode proteins and the RNA molecules that carry out protein synthesis. RNA carries the gene sequence information so that it can be utilized, while the DNA is transmitted when the cell divides. Much of the genome does not encode protein. Variants of a gene, called alleles, arise by mutation. They may differ slightly from one another, but encode the same product. A polymorphism is a site or sequence of DNA that varies in one percent or more of a population.
An allele combination constitutes the genotype. Alleles may be dominant exerting an effect in a single copy or recessive requiring two copies for expression. Chromosomes consist of DNA and protein. The 22 types of autosomes do not include genes that specify sex. The X and Y sex chromosomes bear genes that determine sex.
Genetic determinism is the idea that the expression of an inherited trait cannot be changed. The human genome consists of about 3 billion DNA bases.
Cells differentiate by expressing subsets of genes. Stem cells divide to yield other stem cells and cells that differentiate. DNA profiling can establish identity, relationships, and origins.
Pedigrees are diagrams used to study traits in families. Genetic populations are defined by their collections of alleles, termed the gene pool. Genome comparisons among species reveal evolutionary relationships. Single genes determine Mendelian traits. Multifactorial traits reflect the influence of one or more genes and the environment. In inherited diseases, recurrence risks are predictable and a mutation may be detected before symptoms arise.
Some inherited disorders are more common among certain population groups. Gene therapy attempts to correct mutations. Studying genes and genomes of nonhuman animals can help us understand causes of diseases in humans. Genetic information can be misused. Agriculture is selective breeding. Biotechnology is the use of organisms or their parts for human purposes. A transgenic organism harbors a gene or genes from a different species.
In metagenomics, DNA collected from habitats is used to reconstruct ecosystems. Review Questions 1. Place the following terms in size order, from largest to smallest, based on the structures or concepts they represent: a. DNA e. Distinguish between: a. List four ways that inherited disease differs from other types of illnesses. Cystic fibrosis is a Mendelian trait; height is a multifactorial trait.
How do the causes of these characteristics differ? Mutants are often depicted in the media as being abnormal, ugly, or evil. Why is this not necessarily true? Health insurance forms typically ask for applicants to list existing or preexisting symptoms. How do the results of a genetic test differ from this? Freeman has published by the Griffiths author team, implements an innovative approach to teaching genetics.
Rather than presenting material in historical order, Modern Genetic Analysis, Second Edition integrates molecular genetics with classical genetics. The integrated approach provides students with a concrete foundation in molecules, while simultaneously building an understanding of the more abstract elements of transmission genetics.
Modern Genetic Analysis, Second Editionalso incorporates new pedagogy, improved chapter organization, enhanced art, and an appealing overall design. Opening with a brief overview of key genetic principles, model organisms, and epigenetics, the book goes on to explorethe use of gene mutations and the analysis of gene expression and activity.
A discussion of the genetic structure of natural populations follows, before the interaction of genes during suppression and epistasis, how we study gene networks, and personalized genomics are considered. Drawing on the latest experimental tools, including microarrays, RNAi screens, and bioinformatics approaches, Genetic Analysis provides a state-of-the-art review of the field, but in a truly student-friendly manner. It uses extended case studies and text boxes to augment the narrative, taking the reader right to the forefront of contemporary research, without losing clarity of explanation and insight.
Rather than presenting material in historical order, Modern Genetic Analysis, Second Edition integrates molecular genetics with classical genetics. The integrated approach provides students with a concrete foundation in molecules, while simultaneously building an understanding of the more abstract elements of transmission genetics.
Modern Genetic Analysis, Second Editionalso incorporates new pedagogy, improved chapter organization, enhanced art, and an appealing overall design. In the new edition of this very practical guideto the different techniques and theory behind genomes and genomeanalysis, Sandy Primrose and new author Richard Twyman provide afresh look at this topic. In the light of recent excitingadvancements in the field, the authors have completely revised andrewritten many parts of the new edition with the addition of fivenew chapters.
Aimed at upper level students, it is essential thatin this extremely fast moving topic area the text is up to date andrelevant. Completely revised new edition of an establishedtextbook. Features new chapters and examples from exciting new researchin genomics, including the human genome project. Excellent new co-author in Richard Twyman, also co-author ofthe new edition of hugely popular Principles of GeneManipulation. Accompanying web-page to help students deal with this difficulttopic at www.
The complete sequencing and mapping of the human genome, as well as the genomes of other model organisms, will be the basis for our future understanding of human disease, and will allow us to answer fundamental questions about development and evolution. It is both a protocol manual and a comprehensive information resource. Written by international experts, each chapter presents a state-of-the-art review of a methodology. Methods are fully described and evaluated; their advantages and disadvantages discussed; and their suitability for different investigations considered.
Step-by-step protocols, including computer analyses, are given for essential experimental procedures. The primary focus is on human genetics and the benefits of an understanding of the genome for the diagnosis and treatment of human disease. We make sure that all our files are available in PDF format, which is currently one of the most popular document formats for computers and mobile devices.
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